Background . Hepatic stellate cells (HSCs) are reported to play significant roles in the development of liver fibrosis. Heme oxygenase-1 (HO-1) is a key rate-limiting enzyme, which could decrease collagen synthesis and liver damage. Nevertheless, it was yet elusive towards the function and mechanism of HO-1. Methods . An HO-1 inducer Hemin or an HO-1 inhibitor ZnPP-IX was used to treat the activated HSC-T6, respectively. MTT assay was adopted to detect cell proliferation. Immunocytochemical staining was employed to test the levels of alpha-smooth muscle actin ( α -SMA), peroxisome proliferator-activated receptor- γ (PPAR γ ), and nuclear factor-kappa B (NF-kappa B) levels in HSC-T6. HO-1, PPAR γ , and NF- κ B expression levels were measured by qRT-PCR and Western blotting. ELISA was then used to detect the levels of transforming growth factor- (TGF-) beta 1 (TGF- β 1), interleukin-6 (IL-6), serum hyaluronic acid (HA), and serum type III procollagen aminopeptide (PIIIP). Results . HSC-T6 proliferation was inhibited in Hemin-treated HSCs. The levels of α -SMA, HA, and PIIIP and the production of ECM were lower in Hemin-treated HSCs, whereas those could be rescued by ZnPP-IX. NF- κ B activation was decreased, but PPAR γ expression was increased after HO-1 upregulation. Furthermore, the levels of TGF- β 1 and IL-6, which were downstream of activated NF- κ B in HSC-T6, were reduced. The PPAR-specific inhibitor GW9662 could block those mentioned effects. Conclusions . Our data demonstrated that HO-1 induction could inhibit HSC proliferation and activation by regulating PPAR γ expression and NF- κ B activation directly or indirectly, which makes it a promising therapeutic target for liver fibrosis.

Background & Aims: Hepatocellular carcinoma (HCC) is the leading cause of death in patients with chronic hepatitis. In this international collaboration, we sought to develop a global universal HCC risk score to predict the HCC development for patients with chronic hepatitis. Methods: A total of 17,374 patients, comprising 10,578 treated Asian patients with chronic hepatitis B (CHB), 2,510 treated Caucasian patients with CHB, 3,566 treated patients with hepatitis C virus (including 2,489 patients with cirrhosis achieving a sustained virological response) and 720 patients with non-viral hepatitis (NVH) from 11 international prospective observational cohorts or randomised controlled trials, were divided into a training cohort (3,688 Asian patients with CHB) and 9 validation cohorts with different aetiologies and ethnicities (n = 13,686). Results: We developed an HCC risk score, called the aMAP score (ranging from 0 to 100), that involves only age, male, albumin-bilirubin and platelets. This metric performed excellently in assessing HCC risk not only in patients with hepatitis of different aetiologies, but also in those with different ethnicities (C-index: 0.82-0.87). Cut-off values of 50 and 60 were best for discriminating HCC risk. The 3- or 5-year cumulative incidences of HCC were 0-0.8%, 1.5-4.8%, and 8.1-19.9% in the low- (n = 7,413, 43.6%), medium- (n = 6,529, 38.4%), and high-risk (n = 3,044, 17.9%) groups, respectively. The cut-off value of 50 was associated with a sensitivity of 85.7-100% and a negative predictive value of 99.3-100%. The cut-off value of 60 resulted in a specificity of 56.6-95.8% and a positive predictive value of 6.6-15.7%. Conclusions: This objective, simple, reliable risk score based on 5 common parameters accurately predicted HCC development, regardless of aetiology and ethnicity, which could help to establish a risk score-guided HCC surveillance strategy worldwide. Lay summary: In this international collaboration, we developed and externally validated a simple, objective and accurate prognostic tool (called the aMAP score), that involves only age, male, albumin-bilirubin and platelets. The aMAP score (ranged from 0 to 100) satisfactorily predicted the risk of hepatocellular carcinoma (HCC) development among over 17,000 patients with viral and non-viral hepatitis from 11 global prospective studies. Our findings show that the aMAP score had excellent discrimination and calibration in assessing the 5-year HCC risk among all the cohorts irrespective of aetiology and ethnicity. (C) 2020 European Association for the Study of the Liver. Published by Elsevier B.V.

Objective: To investigate the effect of rosiglitazone (RGZ) on the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and heme oxygenase-1 (HO-1) in hepatic stellate cells (HSCs). Methods: In vitro activated hepatic stellate cell-T6 (HSC-T6) as research subjects were divided into blank control group, RGZ intervention group, and RGZ + ZnPP-IX mutual intervention group. MTT colorimetry method was used to measure the condition of cell proliferation. ELISA was used to detect the content of hyaluronic acid (HA) and type III procollagen peptide (PIIIP) in the cell supernatant. Real-time quantative PCR, western blot and immunocytochemistry were used to detect the relative expression levels of PPARγ, HO-1 mRNA and protein. One-way analysis of variance was used to compare the sample mean between multiple groups, and LSD test was used for comparison between two groups. Results: The proliferation activity of HSC-T6 and the expressions of HA and PIIIP in the RGZ intervention group were significantly lower than those in the blank control group (P ​​< 0.01), but the relative expression levels of PPARγ and HO-1 mRNA and protein were significantly increased compared with the blank control group (PPARγ : 2.97 ± 0.22 vs. 1.07 ± 0.05, 0.96 ± 0.08 vs. 0.31 ± 0.03; HO-1: 4.28 ± 0.73 vs. 1.80 ± 0.36, 1.83 ± 0.26 vs. 0.61 ± 0.09), and the difference was statistically significant (P < 0.01). The proliferation activity of HSC-T6 and the expression of HA and PIIIP was higher in RGZ + ZnPP-IX mutual intervention group as compared with RGZ group (P < 0.05). HO-1 mRNA (3.16 ± 0.38 vs. 4.28 ± 0.73) and protein (1.31 ± 0.17 vs. 1.83 ± 0.26) relative expression levels was decreased, and the difference was statistically significant (P < 0.05). There was no statistically significant difference in the relative expression of PPARγ mRNA and protein (P > 0.05), however, there was a decreasing trend. HO-1 mRNA (1.80 ± 0.36) and protein (0.61 ± 0.09) relative expression was significantly increased in RGZ + ZnPP-IX group as compared to blank control group (P < 0.05). Immunocytochemical staining had consistency with the above results. Conclusion: The effect of rosiglitazone on inducing increased expression of PPARγ, and then inhibiting HSC proliferation activity and collagen production may be realized by regulating its downstream HO-1 expression.

•We study whether Bitcoin is affected by EPU from a risk spillover view.•Both the MVQM-CAViaR and the Granger causality risk test are used.•The risk spillover effect from EPU to Bitcoin is negligible in most conditions.•Our finding is robust to data frequency, the influence of the 2013/12 Bitcoin price crash and instantaneous correlations.•Bitcoin can be acted as a safe-haven or a diversifier under EPU shocks.

The fluctuations of international crude oil markets have caused significant attention around the world and aroused strong interest in the forecasting of the systemic risk in crude oil trade. Based on the oil imported values data of 34 major oil-importing countries from January 2005 to June 2017, we calculate the cross-correlation functions of time lags and construct a sequence of time-evolving oil import correlation networks according to the similarities between countries. The probability distribution of time lag shows that the time lag effect is not sensitive to positive correlations, but obvious for negative correlations. There is a longer time-lag effect in the years when positive correlations are stronger. Further, we use a percolation analysis to quantify the structural change in the correlation network. The key result is that abrupt percolation transition is leading spikes in systemic risk with advance of 3–11 months suggesting that this event could function as an alarm. Therefore, percolation transition in the correlation network of oil-importing countries can be used as a means to estimate signals about future systemic risk. The methodology and results presented in this paper bring a fresh perspective to the study of systemic risk in crude oil importing trade, and they facilitate risk early-warning research in other energy systems that also have interactions among their elements.

Purpose The purpose of this paper is to examine publication characteristics and dynamic evolution of the Industrial Management & Data Systems (IMDS) over the past 25 years from volume 94, issue 1, in 1994 through volume 118, issue 9, in 2018, using a bibliometric analysis, and identify the leading trends that have affected the journal during this time frame. Design/methodology/approach A bibliometric approach was used to provide a basic overview of the IMDS, including distribution of publication and citations, articles citing the IMDS, top-cited papers and publication patterns. Then, a complex network analysis was employed to present the most productive, influential and active authors, institutes and countries/regions. In addition, cluster analysis and alluvial diagram were used to analyze author keywords. Findings This study presents the basic bibliometric results for the IMDS and focuses on exploring its performance over the last 25 years. And it reveals the most productive, influential and active authors, institutes and countries/regions in IMDS. Moreover, this study detects the existence of at least five different keywords clusters and discovers how themes have evolved through the intricate citation relationships in IMDS. Originality/value The main contribution of this paper is the use of multiple analysis techniques from a complex network paradigm to emphasize the time evolving nature of the co-occurrence networks and to explore the variation of the collaboration networks in the IMDS. For the first time, the evolution of research themes is revealed with a purely data-driven approach.

Forecasting the price of crude oil is a challenging task. To improve this forecasting, this paper proposes a novel hybrid method that uses an integrated data fluctuation network (DFN) and several artificial intelligence (AI) algorithms, named DIN-AI model. In the proposed DFN-AI model, a complex network time series analysis technique is performed as a preprocessor for the original data to extract the fluctuation features and reconstruct the original data, and then an artificial intelligence tool, e.g., BPNN, RBFNN or ELM, is employed to model the reconstructed data and predict the future data. To verify these results we examine the daily, weekly, and monthly price data from the crude oil trading hub in Cushing, Oklahoma. Empirical results demonstrate that the proposed DIN-AI models (i.e., DFN-BP, DEN-RBF, and DFN-ELM) perform significantly better than their corresponding single AI models in both the direction and level of prediction. This confirms the effectiveness of our proposed modeling of the nonlinear patterns hidden in crude oil prices. In addition, our proposed DEN-AI methods are robust and reliable and are unaffected by random sample selection, sample frequency, or breaks in sample structure.

EB 病毒是一种属于疱疹病毒家族的双链 DNA 病毒 ,通过唾液传播 ,最初感染口咽和鼻咽上皮细胞[1] ,随后进入深层组织 ,感染 B 淋巴细胞 ,也可以感染 NK 细胞 、T 淋巴细胞和平滑肌细胞[2] . EB 病毒可以引起潜伏感染或溶细胞性感染[3-6] . 儿童 EB 病毒感染多为急性发作 ,经抗病毒治疗后预后好 ,但临床症状很难与其他病毒感染相鉴别[7-8] ,成人感染 EB 病毒后临床表现各异[9-10] ,90％ ～ 95％ 的成人血清中可检测到 EBV 抗体 ,感染后终生携带[5] . EB 病毒感染根据病程可分为急性感染 、慢性感染和 EB 感染相关肿瘤 ,急性感染预后较好 ,随着病程迁延 ,少数急性感染发展为预后较差的慢性感染或肿瘤[11] . 本文回顾性研究山西医科大学第一医院感染病科 2016 年 1 月至 2018 年 1 月 EB 病毒感染患者 ,分析其临床资料 ,为临床诊治提供帮助 .

Heme oxygenase-1 (HO-1) is an antioxidant and cytoprotective protein, which has been proven to alleviate the proliferation of hepatic stellate cells (HSCs) and the development of liver fibrosis. However, the role of HO-1 in HSC apoptosis remains unclear. The aim of the present study was to investigate the effect of HO-1 on HSC apoptosis and its possible underlying mechanisms. HSCs-T6 were incubated with different concentrations of hemin (HO-1 chemical inducer) and Znpp-IX (HO-1 chemical inhibitor) for 12, 24 and 48 h. Cell viability was determined using an MTT assay. HSCs were classified into 4 groups as follows: Control, hemin, Znpp-IX and hemin+Znpp-IX co-treatment groups. Apoptosis was quantitatively measured by Annexin V/propidium iodide double staining and a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. The mRNA and protein expression of HO-1, α-smooth muscle actin, B-cell lymphoma (Bcl)-2, caspase-3 and nuclear factor (NF)-κB p65 were measured using quantitative polymerase chain reaction and western blotting. The levels of tumor growth factor (TGF)-β and interleukin (IL)-6 in HSC supernatants were examined by ELISA. The results demonstrated that HO-1 exerted antiproliferative effects on HSCs in a time- and concentration-dependent manner. Increasing HO-1 expression induced HSC apoptosis in vitro as demonstrated by a significant decrease in Bcl-2 and an increase in caspase-3 expression. Additionally, the expression of NF-κB p65 and its downstream inflammatory factors TGF-β and IL-6 in the HO-1 overexpression group was significantly decreased compared with the control group. Therefore, the present study provided evidence that HO-1 serves an anti-fibrosis role in the liver by enhancing HSC apoptosis, which was partially associated with the regulation of NF-κB and its downstream effectors.

Using the volatility spillover network of Diebold and Yilmaz (2014), we investigate volatility connectedness in the Chinese banking system based on daily range-based volatility series of 14 publicly-traded commercial banks from 2008 to 2016. Both static and dynamic total connectedness show that the 14 commercial banks are highly interconnected. Total directional connectedness (including from-connectedness, to-connectedness and net-connectedness) shows that state-owned commercial banks contribute less to volatility connectedness than joint-stock and city commercial banks, and that city commercial banks are the largest (net-) emitters of volatility connectedness. Statically, we find a positive (negative) rank correlation between size and from-connectedness (to-connectedness and net-connectedness) of banks. Dynamically, however, the positive rank correlation loses its statistical significance and the negative rank correlation disappears completely during the recent global financial crisis and "the 2015-2016 Chinese stock market turbulence." Our findings suggest (i) that a bank might be "too big to fail," but not necessarily "too interconnected to fail" and vice versa, and (ii) that these two cases may coexist conditional on the system being in distress. (C) 2018 Elsevier B.V. All rights reserved.

Background This 5-year follow-up of the CCgenos cross-sectional study aimed to observe real-life outcomes in a cohort of 997 Han Chinese patients with chronic HCV infection and to explore the impacts of HCV genotype, patient characteristics and treatment status. Methods Clinical information and centralized HCV RNA measures were collected every 6/3 months for untreated/treated patients. Overall disease progression was defined as ≥1 of: de novo development of cirrhosis, Child-Turcotte-Pugh score increased by ≥2 points (if cirrhosis at baseline), progression to decompensated cirrhosis, hepatocellular carcinoma (HCC), liver transplant or death. Cox regression assessed risk factors for the time from estimated infection to cirrhosis or HCC. Logistic regression assessed risk factors for incidence rates of cirrhosis and overall disease progression. Results 281 of 514 patients enrolled across China completed 5 years of follow-up. Overall disease progression occurred in 36/364 (9.9%) treated patients and 35/148 (23.6%) untreated patients (odds ratio = 0.35; 95% CI 0.21, 0.59; P<0.0001). Overall disease progression occurred in 6/231 (2.6%) patients achieving sustained virological response at 24 weeks (SVR24) versus 11/82 (13.4%) who did not ( P=0.0002). Cirrhosis development was significantly associated with abnormal aspartate aminotransferase (AST), age ≥40 years, body mass index ≥28 kg/m2, HCV GT1, platelet count <100x109/l, and AST to platelet ratio index (APRI) ≥2 (multivariate Cox regression, P<0.05). HCC was significantly associated with HCV GT1 and platelet count <100x109/l (multivariate Cox regression, P<0.05). Conclusions Achieving SVR24 significantly reduced the probability of overall disease progression but no significant difference was seen for both cirrhosis and HCC during 5 years of follow-up.

Objective: To observe the therapeutic effects and related mechanism of hemin on the progression of hepatic fibrosis in rats. Methods: Sixty male Wistar rats were randomly divided into normal control group, 4-week model group, 6-week model group, hemin inhibitor zinc protoporphyrin-IX (ZnPP-IX) intervention group and hemin intervention group. Hemin intervention group in complex liver fibrosis model was intraperitonealy administered ZnPP-IX or hemin every other day for 2 weeks from the fourth week. The mRNA expression of HO-1, α-smooth muscle actin (α-SMA) and nuclear factor-κB (NF-κB) in the liver tissue was detected by real-time polymerase chain reaction. Immunohistochemistry was used to detect HO-1 and localization of α-SMA expression. Serum hyaluronic acid, propeptide of type III collagen and hepatic transforming growth factor beta (TGFβ), and interleukin 6 (IL-6) expressions were detected by enzyme-linked immunosorbent assay. The content of hydroxyproline in hepatic tissues was measured by alkaline hydrolysis method. One-way ANOVA was used to compare the mean of each group. The difference between the two groups was compared by independent samples t- test. P-values < 0.05 was considered statistically significant. Results: Compared with model groups and ZnPP-IX intervention group, Hemin's intervention significantly increased the expression of HO-1 mRNA (P < 0.01) and protein distribution in liver tissues, while the expression of alpha-SMA mRNA was significantly decreased (P < 0.05) in portal space and areas around the fibrotic septum, and hepatic sinus. Hyp content and serum hyaluronic acid and propeptide of type III collagen decreased significantly (P < 0.05). Meanwhile, NF-κB p65 mRNA expression and the downstream production of TGFβ and IL-6 in Hemin intervention group were also inhibited (P < 0.05). Conclusion: Hemin can significantly inhibit the progression of hepatic fibrosis in rats by up-regulating HO-1 expression, and the inhibiting activity of NF-κB p65 leads to downstream of the inflammatory factors.

Most network research studying the robustness of critical infrastructure networks focuses on a particular aspect and does not take the entire system into consideration. We develop a general methodological framework for studying network robustness from multiple perspectives, i.e., Robustness assessment based on percolation theory, vulnerability analysis, and controllability analysis. Meanwhile, We use this approach to examine the Shanghai subway network in China. Specifically, (1) the topological properties of the subway network are quantitatively analyzed using network theory; (2) The phase transition process of the subway network under both random and deliberate attacks are acquired (3) Critical dense areas that are most likely to be the target of terrorist attacks are identified, vulnerability values of these critical areas are obtained; (4) The minimum number of driver nodes for controlling the whole network is calculated. Results show that the subway network exhibits characteristics similar to a scale-free network with low robustness to deliberate attacks. Meanwhile, we identify the critical area within which disruptions produce large performance losses. Our proposed method can be applied to other infrastructure networks and can help decision makers develop optimal protection strategies.

Objective To investigate the effects of HepG2 and HepG2.2.15 cells steatosis on the mRNA and protein expressions of suppressors of cytokine signaling-3(SOCS-3) and sterol regulatory element binding proteins (SREBP-1c).Methods The cell model of chronic hepatitis B (CHB) combined with nonalcoholic fatty liver disease (NAFLD) was successfully constructed using an oleic acid-induced HepG2 and HepG2.2.15 cells steatosis.Cells were divided into HepG2 cell control group (HepG2 cell control group), HepG2.2.15 cell control group (HepG2.2.15 cell control group), HepG2 cell steatosis group (HepG2 cell steatosis group) and HepG2.2.15 cell steatosis group (HepG2.2.15 cell steatosis group).The expression levels of SOCS-3 and SREBP-1c mRNA were detected by real-time quantitative polymerase chain reaction (PCR).Changes in protein expressions of SOCS-3 and SREBP-1c were measured by western blot.Results SOCS-3 mRNA expression level in HepG2.2.15 cell control group was significantly lower than that in HepG2 cell control group (P<0.01).The level in HepG2 cell steatosis group was also significantly lower than that in HepG2 cell control group (P<0.01).However, the level of SOCS-3 mRNA in HepG2.2.15 cell steatosis group was lower than HepG2.2.15 cell control group with no statistical significance (P=0.173).There was interaction between cells and steatosis (F=25.547, P<0.01).The expression of SREBP-1c mRNA in HepG2.2.15 cell control group was significantly lower than that in HepG2 cell control group (P<0.01), and was significantly higher in HepG2.2.15 cell steatosis group than that in HepG2.2.15 cell control group (P<0.01).There was no significant difference between HepG2 cell steatosis group and HepG2 cell control group (P=1.000).There was interaction between cells and steatosis (F=5.04, P<0.05).Western blot analysis showed that protein levels of SOCS-3 and SREBP-1c in steatosis cells at 48 h and 72 h were significantly higher than those in non-alcoholic steatosis cells.Conclusions Protein expressions of SOCS-3 and SREBP-1c are up-regulated in both steatosis groups.Factorial analysis shows that there is interaction between cells and steatosis.HBV gene could inhibit SOCS-3 mRNA expression and promote the expression of SREBP-1c mRNA in steatosis cells.

Objective To investigate the efficacy and safety of type Y pegylated interferon α -2b (YPegIFNα-2b,40kD) in the treatment of patients with chronic hepatitis C virus genotypes 2/3 infection in arandomized,PegIFNα-2a-controlled phase III clinical trial. Methods A multi-center,randomized,open-label and positive controlled phase III clinical trial was conducted in this study. Chronic hepatitis C (CHC) patients who met inclusion criteria were randomly allocated in a ratio of 2:1 to 2 cohorts and treated with YPegIFNα-2b or PegIFNα-2a (180 μg),respectively,and ribavirin for 24 weeks,and they were all followed-up for 24 weeks after discontinuation of the regimen. The primary efficacy was assessed by sustained virological response (SVR). Results Two hundred fifty-five participants with genotypes 2 or 3 HCV infection were enrolled. Intention-to-treat analysis showed that SVR were 85.4%(95% CI 79.94%-90.94%) and 79.5% (95% CI 70.84%-88.20%) in patients treated with YPegIFNα-2b and PegIFNα-2a,respectively (P=0.2402);95% confidence intervals of rate difference conformed to standard of non-inferiority. Positive predictive value of rapid virological response for SVR was 90.1%;Additionally,there were no significant differences in adverse effects (95.6% vs. 95.2%) and severe adverse effects (3.8% vs. 3.6%) between the YPegIFNα-2b- and control agent-treated patients with CHC. Conclusions YPegIFNα-2b provides an alternative efficacious treatment option in patients with chronic HCV genotypes 2/3 infection as its similar efficacy and safety to PegIFNα-2a in this pilot clinical trial.

Objective To investigate the relationship between the expression of miR-122 in HBV-related acute-on-chronic liver failure (HBV-ACLF) and clinical indicators, and to analyze the role of miR-122 in evaluating the severity and diagnosis of HBV-ACLF. Methods Serum samples from 49 patients with HBV-ACLF, 30 patients with chronic hepatitis B (CHB) and 30 healthy volunteers were collected from the First Affiated Hospital of Shanxi Medical University. The relative expression of miR-122 in each sample was detected by fluorescence real-time quantitative PCR. With the u6 as endogenous control, the relative expression of miR-122 was expressed as 2-ΔCT. Patients with HBV-ACLF were divided into early stage, middle stage and late stage groups according to the severity of clinical manifestations. The levels of miR-122 expression between different groups were compared, and the correlation between the expression of miR-122 and biochemical markers were analyzed, respectively. Furthermore, the role of miR-122 in the progression of HBV-ACLF was analyzed by Unconditional Logistic regression model, thus reflecting the association between miR-122 and disease severity. Receiver operating characteristic curve (ROC) was used to evaluate the value of serum miR-122 in the diagnosis of HBV-ACLF. Results The expression level of miR-122 in serum of patients with HBV-ACLF was significantly higher than those of healthy subjects and patients with CHB (P < 0.001), and the level of miR-122 expression in advanced HBV-ACLF was significantly higher than those of the early and middle stages (P < 0.001, P = 0.048). The serum level of miR-122 in patients with HBV-ACLF was positively correlated with the level of serum total bilirubin (TBil) (r = 0.508, P < 0.001) and negatively correlated with PTA (r =-0.797, P < 0.001). Unconditional Logistic regression model showed that an increase of one unit of relative expression of miR-122 (2-ΔCT) was associated with 5.8％ (95％CI: 1.013-1.104) increase in the risk of progression from HBV-ACLF early stage to middle stage and 13.0％ (95％CI: 1.034-1.235) increase in the risk from early stage to late stage. The ROC analysis showed that the area under the curve (AUC) of disease diagnosis was 0.942 (95％CI: 0.903-0.982), the sensitivity and the specificity were 83.7％ and 86.7％. Conclusions The expression level of miR-122 in serum could be used as a biomarker for the diagnosis and the severity of HBV-ACLF.

Chronic hepatitis B is a progressive disease that can develop into cirrhosis,liver cancer or even liver failure if it is not treated in time.Antiviral therapy is an important means to delay the progression of chronic hepatitis B disease,through long-term inhibition of HBV DNA replication can reduce liver cell inflammation and necrosis,fibrosis,delaying and reducing liver failure,cirrhosis,HCC and other complications,which can improve the life quality and prolong survival time.Based on the data of hepatitis B first-line Antiviral Agents such as entecavir and tenofovir And so on.being used worldwide,this paper expounds the influence of antiviral therapy on the outcome of chronic hepatitis B treatment.

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion: In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.